GENETIC CONTRIBUTIONS TO LEARNING DISABILITIES SUBTYPES

阅读障碍和书写困难是常见的和复杂的疾病，具有长期的教育、经济和社会影响。了解其生物学基础可能会导致更早和更具体的干预。这个项目将通过评估具有学习障碍(LD)特征的家系来调查与阅读困难和书写困难的特定亚型有关的遗传因素。有5个具体目标。1.扩增阅读障碍和/或书写困难家系的DNA文库和细胞系。对先证者的确定(未来五年将有500人)将扩大到9年级，继续招募患有诵读困难和书写困难的先证者，并增加招募仅有书写困难表型的先证者。2.继续确定LD亚型的传播模式。语言表型将扩大到包括形态过程和前一个赠款周期的结果的家族聚集模式和相互依赖，作为数量性状的注意力不集中的共病和计算障碍的共病也将被调查。最有可能有遗传病因的LD亚型将在分离分析中进行评估，以开发用于连锁分析的模型。3.检测学习障碍亚型之间的关联。第1、2、6、7和15号染色体上已进行基因分型的候选区域将被评估是否与LD表型连锁，并将进行全基因组扫描以确定其他候选区域。4.对连锁分析中确定的最有希望的区域进行精细定位，以便进行基因鉴定。5.优化UWLDC数据库，并对数据进行质量控制分析。该项目是与临床核心密切合作进行的，以进行仔细的表型分析，并与统计核心合作进行所有统计遗传分析。通过应用新兴的强大的分析方法，将加快实现这些目标。项目三还与项目一和项目二相联系，将语言表型扩大到包括形态过程。项目III通过对使用FMRS测量作为数量性状的可行性的探索性研究与项目IV相联系。

Dyslexia and dysgraphia are common and complex disorders are common and complex disorders that have long-term educational, economic, and social repercussions. Understanding the biologic basis may lead to earlier and more specific intervention. This project will investigate genetic factors involved in specific subtypes of dyslexia and dysgraphia by evaluating kindreds well-characterized from learning disabilities (LD). There are 5 specific aims. 1. To expand a bank of DNA and cell lines from pedigrees with dyslexia and/or dysgraphia. Ascertainment of probands (500 over the next five years) will be extended to grade 9, for continued recruitment of probands with combined dyslexia and dysgraphia and for increased recruitment of probands with the dysgraphia-only phenotype. 2. To continue to determine transmission patterns of LD subtypes. The language phenotype will be broadened to include morphological processes and the familial aggregation patterns and interdependence of the findings of the previous grant cycle, comorbidity of inattention as a quantitative trait and comorbidity of calculation disability will also be investigated. The LD subphenotypes most likely to have a genetic etiology will be evaluated in segregation analyses to develop models for use in linkage analyses. 3. To detect linkage of learning disabilities subtypes. Candidate regions on chromosomes 1, 2, 6, 7, and 15, already genotyped, will be evaluated for linkage to LD phenotypes and a genome-wide scan will be performed to identify other candidate regions. 4. To perform fine scale mapping of the most promising regions identified in the linkage analyses to enable gene identification. 5. To optimize the UWLDC database and to perform quality control analyses of the data. This Project is carried out in close collaboration with the Clinical Core for the careful phenotyping and with the Statistical Core for all statistical genetic analyses. The goals will be expedited by applying emerging powerful analysis methods. Project III is also linked to Projects I and II in extending the language phenotype to include morphologic processes. Project III is linked to Project IV via an exploratory study of the feasibility of using fMRS measurements as the quantitative trait.